Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis
Summary: Inflammatory bowel disease (IBD) is linked to male fertility disorders, yet the role of gut microbiota dysbiosis remains underexplored. Here, we investigated how dysbiosis contributes to autoimmune epididymo-orchitis in a colitis mouse model induced by CD4+ T cell transfer. We transferred w...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225007692 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849324182931767296 |
|---|---|
| author | Qunxiong Zeng Jin-Chuan Liu Chen Yang Minmin Lyu Dongliang Li William S.B. Yeung Philip C.N. Chiu Tao Zhang Yong-Gang Duan |
| author_facet | Qunxiong Zeng Jin-Chuan Liu Chen Yang Minmin Lyu Dongliang Li William S.B. Yeung Philip C.N. Chiu Tao Zhang Yong-Gang Duan |
| author_sort | Qunxiong Zeng |
| collection | DOAJ |
| description | Summary: Inflammatory bowel disease (IBD) is linked to male fertility disorders, yet the role of gut microbiota dysbiosis remains underexplored. Here, we investigated how dysbiosis contributes to autoimmune epididymo-orchitis in a colitis mouse model induced by CD4+ T cell transfer. We transferred wild-type CD4+ T cells into male Rag1−/− mice, with some groups pretreated with antibiotics or receiving Il-17a−/− or Ccr6−/− CD4+ T cells. Through gut microbiota profiling, histopathology evaluation, immune cell infiltration assessments in the reproductive tissues, and sperm analysis, we observed severe gut dysbiosis, colon inflammation, and reproductive impairments characterized by leukocyte infiltration in mice transferred with wild-type T cells. Interestingly, these impairments were mitigated in groups pretreated with antibiotics or receiving Il-17a−/− cells but not Ccr6−/− CD4+ T cells. These findings highlight that gut microbiota dysbiosis can initiate Th17 cell-mediated reproductive disorders, offering insights for potential therapeutic interventions in IBD-related male infertility. |
| format | Article |
| id | doaj-art-c189af66b00748deb2181e97bb8fc213 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-c189af66b00748deb2181e97bb8fc2132025-08-20T03:48:47ZengElsevieriScience2589-00422025-05-0128511250810.1016/j.isci.2025.112508Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitisQunxiong Zeng0Jin-Chuan Liu1Chen Yang2Minmin Lyu3Dongliang Li4William S.B. Yeung5Philip C.N. Chiu6Tao Zhang7Yong-Gang Duan8Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, China; Department of Obstetrics and Gynaecology, the University of Hong Kong, Pokfulam Road, Hong Kong, ChinaShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, China; Department of Obstetrics and Gynaecology, the University of Hong Kong, Pokfulam Road, Hong Kong, ChinaShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, ChinaShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, ChinaShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, China; Department of Obstetrics and Gynaecology, the University of Hong Kong, Pokfulam Road, Hong Kong, ChinaShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, China; Department of Obstetrics and Gynaecology, the University of Hong Kong, Pokfulam Road, Hong Kong, ChinaShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, China; Department of Obstetrics and Gynaecology, the University of Hong Kong, Pokfulam Road, Hong Kong, ChinaDepartment of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Corresponding authorShenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, the University of Hong Kong - Shenzhen Hospital, Shenzhen 518053, China; Corresponding authorSummary: Inflammatory bowel disease (IBD) is linked to male fertility disorders, yet the role of gut microbiota dysbiosis remains underexplored. Here, we investigated how dysbiosis contributes to autoimmune epididymo-orchitis in a colitis mouse model induced by CD4+ T cell transfer. We transferred wild-type CD4+ T cells into male Rag1−/− mice, with some groups pretreated with antibiotics or receiving Il-17a−/− or Ccr6−/− CD4+ T cells. Through gut microbiota profiling, histopathology evaluation, immune cell infiltration assessments in the reproductive tissues, and sperm analysis, we observed severe gut dysbiosis, colon inflammation, and reproductive impairments characterized by leukocyte infiltration in mice transferred with wild-type T cells. Interestingly, these impairments were mitigated in groups pretreated with antibiotics or receiving Il-17a−/− cells but not Ccr6−/− CD4+ T cells. These findings highlight that gut microbiota dysbiosis can initiate Th17 cell-mediated reproductive disorders, offering insights for potential therapeutic interventions in IBD-related male infertility.http://www.sciencedirect.com/science/article/pii/S2589004225007692Biological sciencesImmunologyImmune systemImmune responseMicrobiology |
| spellingShingle | Qunxiong Zeng Jin-Chuan Liu Chen Yang Minmin Lyu Dongliang Li William S.B. Yeung Philip C.N. Chiu Tao Zhang Yong-Gang Duan Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis iScience Biological sciences Immunology Immune system Immune response Microbiology |
| title | Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis |
| title_full | Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis |
| title_fullStr | Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis |
| title_full_unstemmed | Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis |
| title_short | Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis |
| title_sort | gut microbiota driven pathogenic th17 cells mediated autoimmune epididymo orchitis in a mouse model of colitis |
| topic | Biological sciences Immunology Immune system Immune response Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225007692 |
| work_keys_str_mv | AT qunxiongzeng gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT jinchuanliu gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT chenyang gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT minminlyu gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT dongliangli gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT williamsbyeung gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT philipcnchiu gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT taozhang gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis AT yonggangduan gutmicrobiotadrivenpathogenicth17cellsmediatedautoimmuneepididymoorchitisinamousemodelofcolitis |